National Center for Immunization & Respiratory Diseases Evidence to Recommendations and GRADE for PCV13 Use Among Immunocompetent Adults ≥65 Years Old Almea Matanock, MD, MS Advisory Committee on Immunization Practices February 28, 2019
Current Adult Pneumococcal Vaccine Recommendations In 2012 ACIP recommended PCV13 in series with PPSV23 for adults ≥19 years old with immunocompromising conditions – Not currently being re-evaluated In 2014 ACIP recommended PCV13 in series with PPSV23 for all PCV13- naïve adults ≥65 years old with the following considerations: – Short term use warranted because of the remaining PCV13-type disease burden – Long term utility may be limited due to anticipated indirect effects from pediatric PCV13 use
Policy Question Should PCV13 be administered routinely to all immunocompetent adults aged ≥65 years in the context of indirect effects from pediatric PCV use experienced to date? – Population : Immunocompetent adults ≥65 years old, with and without chronic medical conditions Intervention : PCV13 at ≥65 years old in series with PPSV23, in the context of – indirect effects – Comparison(s) : PPSV23 alone at ≥65 years old, in the context of indirect effects – Outcomes : invasive pneumococcal disease (IPD), pneumonia, mortality, and PCV13 safety
ACIP Evidence to Recommendation (EtR) Framework Statement of problem Public health priority – – Burden of disease Benefits and harms Balance of desirable and undesirable effects – Certainty in evidence – Values and preferences of target population Acceptability to stakeholders Resource use – Health economic analyses Feasibility – Implementation considerations
Evidence to Recommendations Statement of problem Benefits and harms with GRADE Values and preferences of target population Acceptability to stakeholders Resource use Feasibility
Context: Indirect Effects from Pediatric PCV Use Experienced Among Adults ≥65 Years Old Nine-fold reduction in vaccine-type invasive pneumococcal disease (IPD) in the US since pediatric PCV (PCV7 and PCV13 combined) introduction 1 – Indirect effects from PCV13 alone led to a 3 fold reduction (2010–2014) – Plateau in incidence since 2014 (combined direct and indirect effects) Similar reductions seen in IPD in Europe since pediatric PCV13 introduction 2 Decline 77% in PCV7 - type and 38% PCV13non7 - type IPD (2009 – 2015) – 1 Active Bacterial Core Surveillance, https://www.cdc.gov/abcs/reports - findings/surv -reports.html, comparing 2000 to 2014 2 Hanquet et al. 2018
Context: Indirect Effects from Pediatric PCV Use Experienced Among Adults ≥65 Years Old Most studies demonstrate a reduction in all-cause pneumonia since introduction of PCVs for children in 2000 1 – In the U.K. PCV7- type pneumonia declined by 88% and PCV13non7 -type pneumonia declined by 30% (2008 –2013) 2 – In the U.S. since pediatric PCV13 introduction, pneumococcal pneumonia hospitalizations have declined (2010–2014) 3 Pneumococcal Pneumonia Among Adults 3 Rate Ratio (95%CI) 1 Tsaban et al. 2017 2 Rodrigo et al. 2015 3 Lessa ACIP October 2018
Vaccine Coverage: Percentage of Medicare beneficiaries aged ≥65 years with claims submitted for pneumococcal vaccination — United States, Sept 2009–Sept 2017 * Each enrollment period extends from September 19 of the first year through September 18 of the subsequent year, with the exce ption of the 2011-12 period, which ends on October 12, 2012, corresponding to the date of publication of the first recommendation for the use of 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults with certain immunocompromising conditions; denominators include all beneficiaries continuously enrolled in Medicare Parts A and B for the duration of the enrollment period. https://www.cdc.gov/vaccines/imz - managers/coverage/adultvaxview/pubs - resources/pcv13 -medicare-beneficiaries.html
Summary: Vaccine-Preventable Disease Burden (PCV13) PCV13- type IPD incidence among adults ≥65 years in 2015 –2017 – Incidence plateaued at 5/100,000 – PCV13 serotypes account for 20% of all IPD plus an addition 3% including 6C – Common PCV13 serotypes (% of PCV13 - types): 3 (66%), 19A (13%), 7F (13%), 19F (12%) PCV13- type pneumonia incidence among adults ≥65 years in 2015 – 2016 Incidence estimates range across studies 17 + to 76/100,000 – – PCV13 serotypes account 3.7% of all -cause pneumonia – Common PCV13 serotypes (% of PCV13 - types): 3 (37%), 19A (28%), 6A (12%), 5 (9%), 7F (7%) + Estimated by applying the %PCV13 - type IPD to the non-invasive pneumococcal pneumonia (NIPP) incidence estimate from the Surveillance for Non-invasive Pneumococcal Pneumonia (SNiPP)
Remaining PCV13-type Disease Burden Compared to Other Vaccine -Preventable Diseases Incidence Adult Vaccine Disease Outcome per 100,000 Recommendation Pneumococcal Invasive and non-invasive PCV13-type 76 ≥65 years old pneumonia hospitalization among ≥65 years old Herpes zoster Herpes zoster cases among 50 year olds 530 ≥50 years old (incidence increases with age) Influenza Laboratory confirmed influenza hospitalization 437 Universal, all adults among ≥65 years old in the 2017 -2018 season Meningococcal Serogroup B meningococcal meningitis among 0.14 Individual clinical 16 –23 year olds decision for healthy 16 –23 year olds
Evidence to Recommendations Statement of problem—Work Group Perspective Benefits and harms with GRADE Values and preferences of target population Acceptability to stakeholders Resource use Feasibility
Burden of Disease PCV13-type disease reduced through indirect effects but burden still remains in older adults Uncertainty about the burden of PCV13-type pneumococcal pneumonia Since 2014 recommendation, at the population level, no further reductions in IPD, and inconsistent results from pneumonia impact studies Question : Is the PCV13 -type disease burden still of public health importance? Judgement:
ACIP EtR Framework Elements Statement of problem Benefits and harms with GRADE Values and preferences of target population Acceptability to stakeholders Resource use Feasibility
Policy Question Should PCV13 be administered routinely to all immunocompetent adults aged ≥65 years in the context of indirect effects from pediatric PCV use experienced to date? – Population : Immunocompetent adults ≥65 years old, with and without chronic medical conditions Intervention : PCV13 at ≥65 years old in series with PPSV23, in the context of – indirect effects – Comparison(s) : PPSV23 alone at ≥65 years old, in the context of indirect effects – Outcomes : invasive pneumococcal disease (IPD), pneumonia, mortality, and PCV13 safety
Outcomes of Interest Type Outcomes Importance PCV13- type IPD Critical PCV13-type non-bacteremic pneumococcal pneumonia (NIPP) Critical Benefits PCV13-type disease mortality Critical Harms Serious adverse events associated with PCV13 Critical Measures of Effect Evaluated: Efficacy/effectiveness: individual -level effects associated with PCV13 use (PCV13 direct effects) Impact: population level changes in disease outcomes associated with PCV13 use (PCV13 direct and indirect effects)
Evidence Retrieval Systematic review of studies from Medline, Embase , CINAHL, Cochrane, and clinicalstrials.gov databases using search string : (Pneumococcal Vaccin*) OR (pneumococcus vaccin*) OR (pneumonia* vaccin*) OR – PCV13 OR pneumovax OR PPSV23 OR prevnar* OR pnu- immune AND senior* OR aged OR older adult* OR elderly OR (over 65) OR (older 65) OR >=65 OR =>65 Dates January 1, 2014 to July 3, 2018 Efforts made to obtain unpublished or other relevant data – Presentations to the work group from industry and independent researchers
Exclusion Criteria Observational studies Low (<20%) PCV13 coverage in the population studied – Not applicable to the U.S. population (i.e. low pediatric vaccine coverage, no pediatric – PCV13 program, low income country) Safety studies – PCV13 co-administered with other vaccines* – Randomized control trials (RCTs) with comparison groups other than PPSV23 or placebo *included in the initial review process, but because SAEs could not be attributed to a single vaccine when vaccines were co - administered we excluded these studies from GRADE
Review Process Title and abstract Records excluded (n=1,883 ) screening (other population, outcomes, or vaccines) (n=2,239) Unpublished data identified (n=8) Full- text article Articles excluded (n=344) screening (other population, outcomes, or vaccines) ( n=364) Studies included in GRADE analysis (n=20)
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